tbuckley/cabot-search huggingface dataset:
Resident T <sub>H</sub> 2 cells orchestrate adipose tissue remodeling at a site adjacent to infection
Authors: Agnieszka M. Kabat, Alexandra Hackl, David E. Sanin, Patrice Zeis, Katarzyna M. Grzes, Francesc Baixauli, Ryan Kyle, George Caputa, Joy Edwards-Hicks, Matteo Villa, Nisha Rana, Jonathan D. Curtis, Angela Castoldi, Jovana Cupovic, Leentje Dreesen, Maria Sibilia, J. Andrew Pospisilik, Joseph F. Urban, Dominic Grün, Erika L. Pearce, Edward J. Pearce
Journal: Science Immunology (2022)

Type 2 immunity is associated with adipose tissue (AT) homeostasis and infection with parasitic helminths, but whether AT participates in immunity to these parasites is unknown. We found that the fat content of mesenteric AT (mAT) declined in mice during infection with a gut-restricted helminth. This was associated with the accumulation of metabolically activated, interleukin-33 (IL-33), thymic stromal lymphopoietin (TSLP), and extracellular matrix (ECM)-producing stromal cells. These cells shared transcriptional features, including the expression of Dpp4 and Pi16, with multipotent progenitor cells (MPC) that have been identified in numerous tissues and are reported to be capable of differentiating into fibroblasts and adipocytes. Concomitantly, mAT became infiltrated with resident T helper 2 (TH2) cells that responded to TSLP and IL-33 by producing stromal cell-stimulating cytokines, including transforming growth factor β1 (TGFβ1) and amphiregulin. These TH2 cells expressed genes previously associated with type 2 innate lymphoid cells (ILC2), including Nmur1, Calca, Klrg1, and Arg1, and persisted in mAT for at least 11 months after anthelmintic drug-mediated clearance of infection. We found that MPC and TH2 cells localized to ECM-rich interstitial spaces that appeared shared between mesenteric lymph node, mAT, and intestine. Stromal cell expression of epidermal growth factor receptor (EGFR), the receptor for amphiregulin, was required for immunity to infection. Our findings point to the importance of MPC and TH2 cell interactions within the interstitium in orchestrating AT remodeling and immunity to an intestinal infection.
Depletion of exhausted alloreactive T cells enables targeting of stem-like memory T cells to generate tumor-specific immunity
Authors: Simone A. Minnie, Olivia G. Waltner, Kathleen S. Ensbey, Nicole S. Nemychenkov, Christine R. Schmidt, Shruti S. Bhise, Samuel R. W. Legg, Gabriela Campoy, Luke D. Samson, Rachel D. Kuns, Ting Zhou, John D. Huck, Slavica Vuckovic, Danniel Zamora, Albert Yeh, Andrew Spencer, Motoko Koyama, Kate A. Markey, Steven W. Lane, Michael Boeckh, Aaron M. Ring, Scott N. Furlan, Geoffrey R. Hill
Journal: Science Immunology (2022)

Some hematological malignancies such as multiple myeloma are inherently resistant to immune-mediated antitumor responses, the cause of which remains unknown. Allogeneic bone marrow transplantation (alloBMT) is the only curative immunotherapy for hematological malignancies due to profound graft-versus-tumor (GVT) effects, but relapse remains the major cause of death. We developed murine models of alloBMT where the hematological malignancy is either sensitive [acute myeloid leukemia (AML)] or resistant (myeloma) to GVT effects. We found that CD8
Fucoidan-based dual-targeting mesoporous polydopamine for enhanced MRI-guided chemo-photothermal therapy of HCC via P-selectin-mediated drug delivery
Authors: Gaofeng Shu, Lin Shen, Jiayi Ding, Junchao Yu, Xiaoxiao Chen, Xiaoju Guo, Enqi Qiao, Yaning Chen, Chenying Lu, Zhongwei Zhao, Yongzhong Du, Minjiang Chen, Jiansong Ji
Journal: Asian Journal of Pharmaceutical Sciences (2022)

The development of novel theranostic agents with outstanding diagnostic and therapeutic performances is still strongly desired in the treatment of hepatocellular carcinoma (HCC). Here, a fucoidan-modified mesoporous polydopamine nanoparticle dual-loaded with gadolinium iron and doxorubicin (FMPDA/Gd3+/DOX) was prepared as an effective theranostic agent for magnetic resonance imaging (MRI)-guided chemo-photothermal therapy of HCC. It was found that FMPDA/Gd3+/DOX had a high photothermal conversion efficiency of 33.4% and excellent T1−MRI performance with a longitudinal relaxivity (r1) value of 14.966 mM−1·s − 1. Moreover, the results suggested that FMPDA/Gd3+/DOX could effectively accumulate into the tumor foci by dual-targeting the tumor-infiltrated platelets and HCC cells, which resulted from the specific interaction between fucoidan and overexpressed p-selectin receptors. The excellent tumor-homing ability and MRI-guided chemo-photothermal therapy therefore endowed FMPDA/Gd3+/DOX with a strongest ability to inhibit tumor growth than the respective single treatment modality. Overall, our study demonstrated that FMPDA/Gd3+/DOX could be applied as a potential nanoplatform for safe and effective cancer theranostics
Indications, trends, and perioperative outcomes of minimally invasive and open liver surgery in non-obese and obese patients: An international multicentre propensity score matched retrospective cohort study of 9963 patients
Authors: Giuseppe Zimmitti, Jasper P. Sijberden, Daniel Osei-Bordom, Nadia Russolillo, Davit Aghayan, Jacopo Lanari, Federica Cipriani, Santi López-Ben, Fernando Rotellar, David Fuks, Mathieu D'Hondt, John N. Primrose, Burak Görgec, Andrea Benedetti Cacciaguerra, Ravi Marudanayagam, Serena Langella, Marco Vivarelli, Andrea Ruzzenente, Marc G. Besselink, Adnan Alseidi, Mikhail Efanov, Felice Giuliante, Ibrahim Dagher, Elio Jovine, Fabrizio di Benedetto, Luca A. Aldrighetti, Umberto Cillo, Bjφrn Edwin, Alessandro Ferrero, Robert P. Sutcliffe, Mohammed Abu Hilal
Journal: International Journal of Surgery (2022)

Despite the worldwide increase of both obesity and the use of minimally invasive liver surgery (MILS), evidence regarding the safety and eventual benefits of MILS in obese patients is scarce. The aim of this study was therefore to compare the outcomes of non-obese and obese patients (BMI 18.5-29.9 and BMI≥30, respectively) undergoing MILS and OLS, and to assess trends in MILS use among obese patients.In this retrospective cohort study, patients operated at 20 hospitals in eight countries (2009-2019) were included and the characteristics and outcomes of non-obese and obese patients were compared. Thereafter, the outcomes of MILS and OLS were compared in both groups after propensity-score matching (PSM). Changes in the adoption of MILS during the study period were investigated.Overall, 9963 patients were included (MILS: n = 4687; OLS: n = 5276). Compared to non-obese patients (n = 7986), obese patients(n = 1977) were more often comorbid, less often received preoperative chemotherapy or had a history of previous hepatectomy, had longer operation durations and more intraoperative blood loss (IOBL), paralleling significantly higher rates of wound- and respiratory-related complications. After PSM, MILS, compared to OLS, was associated, among both non-obese and obese patients, with less IOBL (200 ml vs 320 ml, 200 ml vs 400 ml, respectively), lower rates of transfusions (6.6% vs 12.8%, 4.7% vs 14.7%), complications (26.1% vs 35%, 24.9% vs 34%), bile leaks(4% vs 7%, 1.8% vs 4.9%), liver failure (0.7% vs 2.3%, 0.2% vs 2.1%), and a shorter length of stay(5 vs 7 and 4 vs 7 days). A cautious implementation of MILS over time in obese patients (42.1%-53%, p < .001) was paralleled by stable severe morbidity (p = .433) and mortality (p = .423) rates, despite an accompanying gradual increase in surgical complexity.MILS is increasingly adopted and associated with perioperative benefits in both non-obese and obese patients.
Computational Approaches and Challenges in Spatial Transcriptomics
Authors: Shuangsang Fang, Bichao Chen, Yong Zhang, Haixi Sun, Longqi Liu, Shiping Liu, Yuxiang Li, Xun Xu
Journal: Genomics Proteomics & Bioinformatics (2022)

The development of spatial transcriptomics (ST) technologies has transformed genetic research from a single-cell data level to a two-dimensional spatial coordinate system and facilitated the study of the composition and function of various cell subsets in different environments and organs. The large-scale data generated by these ST technologies, which contain spatial gene expression information, have elicited the need for spatially resolved approaches to meet the requirements of computational and biological data interpretation. These requirements include dealing with the explosive growth of data to determine the cell-level and gene-level expression, correcting the inner batch effect and loss of expression to improve the data quality, conducting efficient interpretation and in-depth knowledge mining both at the single-cell and tissue-wide levels, and conducting multi-omics integration analysis to provide an extensible framework toward the in-depth understanding of biological processes. However, algorithms designed specifically for ST technologies to meet these requirements are still in their infancy. Here, we review computational approaches to these problems in light of corresponding issues and challenges, and present forward-looking insights into algorithm development.
Vps37a regulates hepatic glucose production by controlling glucagon receptor localization to endosomes
Authors: Revathi Sekar, Karsten Motzler, Yun Kwon, Aaron Novikoff, Julia Jülg, Bahar Najafi, Surui Wang, Anna-Luisa Warnke, Susanne Seitz, Daniela Hass, Sofiya Gancheva, Sabine Kahl, Bin Yang, Brian Finan, Kathrin Schwarz, Juergen G. Okun, Michael Roden, Matthias Blüher, Timo D. Müller, Natalie Krahmer, Christian Behrends, Oliver Plettenburg, Marta Miaczynska, Stephan Herzig, Anja Zeigerer
Journal: Cell Metabolism (2022)

During mammalian energy homeostasis, the glucagon receptor (Gcgr) plays a key role in regulating both glucose and lipid metabolisms. However, the mechanisms by which these distinct signaling arms are differentially regulated remain poorly understood. Using a Cy5-glucagon agonist, we show that the endosomal protein Vps37a uncouples glucose production from lipid usage downstream of Gcgr signaling by altering intracellular receptor localization. Hepatocyte-specific knockdown of Vps37a causes an accumulation of Gcgr in endosomes, resulting in overactivation of the cAMP/PKA/p-Creb signaling pathway to gluconeogenesis without affecting β-oxidation. Shifting the receptor back to the plasma membrane rescues the differential signaling and highlights the importance of the spatiotemporal localization of Gcgr for its metabolic effects. Importantly, since Vps37a knockdown in animals fed with a high-fat diet leads to hyperglycemia, although its overexpression reduces blood glucose levels, these data reveal a contribution of endosomal signaling to metabolic diseases that could be exploited for treatments of type 2 diabetes.
The rheumatoid arthritis drug auranofin lowers leptin levels and exerts antidiabetic effects in obese mice
Authors: Aaron R. Cox, Peter M. Masschelin, Pradip K. Saha, Jessica B. Felix, Robert Sharp, Zeqin Lian, Yan Xia, Natasha Chernis, David A. Bader, Kang Ho Kim, Xin Li, Jun Yoshino, Xin Li, Gang Li, Zheng Sun, Huaizhu Wu, Cristian Coarfa, David D. Moore, Samuel Klein, Kai Sun, Sean M. Hartig
Journal: Cell Metabolism (2022)
Does Clinical Evidence of Heterogeneity Impact Treatment Selection? A Case Study of Abiraterone for Metastatic Prostate Cancer
Authors: Boshen Jiao, Yaw A. Nyame, Josh J. Carlson, Louis P. Garrison, Anirban Basu
Journal: Journal of the National Comprehensive Cancer Network (2022)

Two pivotal randomized controlled trials (RCTs) demonstrate that abiraterone acetate + prednisone (AAP) combined with androgen deprivation therapy (ADT) significantly extends the survival of men with metastatic hormone-sensitive prostate cancer (mHSPC) compared with ADT alone. Their subgroup analyses indicate that the survival benefit is significant for younger men but not older men. We aimed to assess whether publication of the RCTs was associated with differential real-world AAP utilization by age groups.Using TriNetX electronic medical records data collected from 43 healthcare organizations across the United States, we performed a difference-in-differences event study among men with newly diagnosed mHSPC observed from June 2014 to June 2019. Eligible subjects were identified based on a comprehensive published algorithm. We analyzed the change in utilization rate of AAP before versus after publication of the RCTs among men aged &lt;70 years versus ≥70 years, adjusting for demographic factors and clinical conditions.Our study included 6,888 men with newly diagnosed mHSPC with 12,738 observations, of whom 46% were aged &lt;70 years. The prepublication trends of AAP utilization were similar between the age groups, whereas publication of the RCTs was associated with a 3.5% higher adjusted uptake rate of AAP among younger men (95% CI, 1.2%-5.8%) relative to older men. This estimate reflects an uptake rate nearly 3 times higher than would have been expected had younger men followed the same utilization trends as older men. The estimates remained consistent throughout the postpublication period.Our study suggests that publication of the RCTs was associated with faster uptake of AAP among younger versus older men with newly diagnosed mHSPC, despite the absence of clinical guidance for differential treatment selection. This finding highlights the importance of confirmatory studies among older men, considering the uncertainties of subgroup analyses in RCTs.
Incident Cardiovascular Diseases Among Survivors of High-Risk Stage II–III Colorectal Cancer: A Cluster-Wide Cohort Study
Authors: Shing Fung Lee, Pui Lam Yip, Balamurugan A. Vellayappan, Cheng Ean Chee, Lea Choung Wong, Eric Yuk-Fai Wan, Esther Wai-Yin Chan, Chak-Fei Lee, Francis Ann-Shing Lee, Miguel Angel Luque-Fernandez
Journal: Journal of the National Comprehensive Cancer Network (2022)

The incidence and survival of colorectal cancer (CRC) are increasing. There is an increasing number of long-term survivors, many of whom are elderly and have comorbidities. We conducted a population-based study in Hong Kong to assess the long-term cardiovascular disease (CVD) incidence associated with adjuvant fluoropyrimidine-based chemotherapy among CRC survivors.Using the population-based electronic medical database of Hong Kong, we identified adults who were diagnosed with high-risk stage II-III CRC and treated with radical surgery followed by adjuvant fluoropyrimidine-based chemotherapy between 2010 and 2019. We evaluated the cause-specific cumulative incidence of CVD (including ischemic heart disease, heart failure, cardiomyopathy, and stroke) using the flexible parametric competing risk modeling framework. The control group without a history of CVD was selected from among a noncancer random sample from primary care clinics in the same geographic area.We analyzed 1,037 treated patients with CRC and 5,078 noncancer controls. The adjusted cause-specific hazard ratio (HR) for CVD in the cancer cohort compared with the control group was 2.11 (95% CI, 1.39-3.20). The 1-, 5-, and 10-year cause-specific cumulative incidences were 2.0%, 4.5%, and 5.4% in the cancer cohort versus 1.2%, 3.0%, and 3.8% in the control group, respectively. Age at cancer diagnosis (HR per 5-year increase, 1.16; 95% CI, 1.08-1.24), male sex (HR, 1.40; 95% CI, 1.06-1.86), comorbidity (HR, 1.88; 95% CI, 1.36-2.61 for 1 comorbidity vs none, and HR, 6.61; 95% CI, 4.55-9.60 for ≥2 comorbidities vs none), diabetes (HR, 1.38; 95% CI, 1.04-1.84), hypertension (HR, 3.27; 95% CI, 2.39-4.50), and dyslipidemia/hyperlipidemia (HR, 2.53; 95% CI, 1.68-3.81) were associated with incident CVD.Exposure to adjuvant fluoropyrimidine-based chemotherapy was associated with an increased risk of CVD among survivors of high-risk stage II-III CRC. Cardiovascular risk monitoring of this group throughout cancer survivorship is advisable.
Clinicopathological Features and Outcomes Comparing Patients With Invasive Ductal and Lobular Breast Cancer
Authors: Steffi Oesterreich, Azadeh Nasrazadani, Jian Zou, Neil Carleton, Tiffany Onger, Matthew D Wright, Yujia Li, Kathryn Demanelis, Bhuvaneswari Ramaswamy, George Tseng, Adrian V Lee, Nicole Williams, Megan Kruse
Journal: JNCI Journal of the National Cancer Institute (2022)

Abstract Background There is increasing interest in better understanding the biology and clinical presentation of invasive lobular cancer (ILC), which is the most common special histological subtype of breast cancer. Limited large contemporary data sets are available allowing comparison of clinicopathologic features between ILC and invasive ductal cancer (IDC). Methods The Great Lakes Breast Cancer Consortium was formed to compare clinical behavior of ILC (n = 3617) and IDC (n = 30 045) from 33 662 patients treated between 1990 and 2017 at 3 large clinical centers. We used Kaplan-Meier analysis, Cox proportional hazards modeling, and propensity score matching to evaluate treatment differences and outcomes. All statistical testing used 2-sided P values. Results Compared with IDC, patients with ILC were more frequently diagnosed at later stages and with more lymph node involvement (corrected P &amp;lt; .001). Estrogen receptor–positive ILCs were of lower grade (grade 1 and 2: 90% in ILC vs 72% in IDC) but larger in size (T3 and 4: 14.3% in ILC vs 3.4% in IDC) (corrected P &amp;lt; .001), and since 1990, the mean ILC size detected at diagnosis increased yearly. Patients with estrogen receptor (ER)–positive ILC underwent statistically significantly more mastectomies compared with ER-positive IDC (57% vs 46%). Using Kaplan-Meier analysis, patients with ER-positive ILC had statistically significantly worse disease-free survival and overall survival than ER-positive IDC although 6 times more IDCs were classified as high risk by OncotypeDx Breast Recurrence Score assay. Conclusions This large, retrospective, collaborative analysis with 3 clinical centers identified meaningful differences in clinicopathological features between ILC and IDC, providing further evidence that these are 2 different entities requiring different clinical management.
Isocitrate dehydrogenase (IDH) mutant gliomas: A Society for Neuro-Oncology (SNO) consensus review on diagnosis, management, and future directions
Authors: Julie J Miller, L Nicolas Gonzalez Castro, Samuel McBrayer, Michael Weller, Timothy Cloughesy, Jana Portnow, Ovidiu Andronesi, Jill S Barnholtz-Sloan, Brigitta G Baumert, Mitchell S Berger, Wenya Linda Bi, Ranjit Bindra, Daniel P Cahill, Susan M Chang, Joseph F Costello, Craig Horbinski, Raymond Y Huang, Robert B Jenkins, Keith L Ligon, Ingo K Mellinghoff, L Burt Nabors, Michael Platten, David A Reardon, Diana D Shi, David Schiff, Wolfgang Wick, Hai Yan, Andreas von Deimling, Martin van den Bent, William G Kaelin, Patrick Y Wen
Journal: Neuro-Oncology (2022)

Isocitrate dehydrogenase (IDH) mutant gliomas are the most common adult, malignant primary brain tumors diagnosed in patients younger than 50, constituting an important cause of morbidity and mortality. In recent years, there has been significant progress in understanding the molecular pathogenesis and biology of these tumors, sparking multiple efforts to improve their diagnosis and treatment. In this consensus review from the Society for Neuro-Oncology (SNO), the current diagnosis and management of IDH-mutant gliomas will be discussed. In addition, novel therapies, such as targeted molecular therapies and immunotherapies, will be reviewed. Current challenges and future directions for research will be discussed.
Differential Detection of Hepatic Metastases on 68Ga-DOTATATE PET/CT and 177Lu-DOTATATE SPECT/CT
Authors: Hanan Zahed, Jean-Mathieu Beauregard, Gad Abikhzer, Christopher Rush, Stephan Probst
Journal: Clinical Nuclear Medicine (2022)

68 Ga-DOTATATE PET/CT is indicated for selecting patients for peptide receptor radionuclide therapy (PRRT). Although highly sensitive, the detectability of smaller lesions, particularly in the liver, is lower. We present the case of a 58-year-old man with metastatic well-differentiated pancreatic neuroendocrine tumor whose MRI revealed progression of hepatic metastases. 68 Ga-DOTATATE PET/CT performed to determine eligibility for PRRT did not demonstrate DOTATATE-avid disease within the liver. 18 F-FDG PET/CT was also negative at the liver and the patient proceeded to 177 Lu-DOTATATE PRRT, where multi-time point posttherapy planar imaging and SPECT/CT showed intense uptake in the known liver metastases.
Sporadic Cerebellar Hemangioblastoma With Strong SSTR Expression on 68Ga-DOTANOC PET/CT
Authors: Indraja D. Dev, Venkatesh Rangarajan, Ameya D. Puranik, Archi Agrawal, Sneha Shah, Ayushi Sahay, Nilendu C. Purandare
Journal: Clinical Nuclear Medicine (2022)

Sporadic cerebellar hemangioblastomas are rare with majority of these tumors presenting as a part of von Hippel-Lindau syndrome. We demonstrate an unusual case of a symptomatic sporadic cerebellar hemangioblastoma mimicking a meningioma on MRI and 68 Ga-DOTANOC PET imaging.
Machine Learning Model to Predict Diagnosis of Mild Cognitive Impairment by Using Radiomic and Amyloid Brain PET
Authors: Andrea Ciarmiello, Elisabetta Giovannini, Sara Pastorino, Ornella Ferrando, Franca Foppiano, Antonio Mannironi, Antonio Tartaglione, Giampiero Giovacchini
Journal: Clinical Nuclear Medicine (2022)

Purpose The study aimed to develop a deep learning model for predicting amnestic mild cognitive impairment (aMCI) diagnosis using radiomic features and amyloid brain PET. Patients and Methods Subjects (n = 328) from the Alzheimer’s Disease Neuroimaging Initiative database and the EudraCT 2015-001184-39 trial (159 males, 169 females), with a mean age of 72 ± 7.4 years, underwent PET/CT with 18 F-florbetaben. The study cohort consisted of normal controls (n = 149) and subjects with aMCI (n = 179). Thirteen gray-level run-length matrix radiomic features and amyloid loads were extracted from 27 cortical brain areas. The least absolute shrinkage and selection operator regression was used to select features with the highest predictive value. A feed-forward neural multilayer network was trained, validated, and tested on 70%, 15%, and 15% of the sample, respectively. Accuracy, precision, F1-score, and area under the curve were used to assess model performance. SUV performance in predicting the diagnosis of aMCI was also assessed and compared with that obtained from the machine learning model. Results The machine learning model achieved an area under the receiver operating characteristic curve of 90% (95% confidence interval, 89.4–90.4) on the test set, with 80% and 78% for accuracy and F1-score, respectively. The deep learning model outperformed SUV performance (area under the curve, 71%; 95% confidence interval, 69.7–71.4; 57% accuracy, 48% F1-score). Conclusions Using radiomic and amyloid PET load, the machine learning model identified MCI subjects with 84% specificity at 81% sensitivity. These findings show that a deep learning algorithm based on radiomic data and amyloid load obtained from brain PET images improves the prediction of MCI diagnosis compared with SUV alone.
18F-Flutemetamol PET/CT for Transthyretin Amyloid Cardiomyopathy
Authors: Eun Ji Han, Yeoun Eun Sung, Mi-Hyang Jung, Joo Hyun O, Jong-Chan Youn
Journal: Clinical Nuclear Medicine (2022)

We report 18 F-flutemetamol PET/CT finding in an 88-year-old man with cognitive impairment and transthyretin amyloid cardiomyopathy. Early phase PET/CT images showed significantly increased myocardial uptake, but there was no myocardial uptake in delayed phase PET/CT images. A dual-time-point amyloid PET/CT imaging may be helpful to diagnose and differentiate subtypes of amyloid cardiomyopathy in patients with suspected cardiac amyloidosis.
Chronic Gastritis Mimicking Malignancy on 68Ga-FAPI-04 PET/CT
Authors: Ediz Beyhan, Özge Erol Fenercioğlu, Enver Yarikkaya, Tevfik Fikret Çermik, Nurhan Ergül
Journal: Clinical Nuclear Medicine (2022)

We present 2 patients mimicking malignancy with intense gastric 68 Ga-FAPI-04 uptake on PET/CT. Both patients showed low to moderate 18 F-FDG uptake. Histopathology revealed chronic active gastritis. Chronic gastritis may resemble gastric malignancies by showing false-positive 68 Ga-FAPI-04 uptake.